Enhancement of murine susceptibility to oral lactate dehydrogenase-elevating virus infection by non-steroidal anti-inflammatory agents, and antagonism by misoprostol

Abstract

The murine lactate dehydrogenase-elevating virus (LDV) was used to study the effects of prostaglandin-acting agents on mucosal resistance to virus infection. Mice treated with non-steroidal anti-inflammatory drugs (NSAIDs) prior to oral exposure to LDV demonstrated a reduction in the mucosal barrier to LDV infection. Histological studies indicated that these NSAID effects were not a result of gross or microscopic tissue damage. The effects of two NSAIDs, indomethacin and diclofenac, were inhibited by co-treatment of mice with misoprostol, a synthetic PGE1 analog. The ability of misoprostol to modulate NSAID effects was not due to direct antiviral activity or to actions on LDV-permissive macrophages. These results show that the mammalian mucosal barrier to virus infection is prostaglandin-sensitive, and provide a model for the study of resistance to viral infection.